Associations of endocrine disrupting chemicals with anogenital distance across infancy

Pregnant women are ubiquitously exposed to endocrine disrupting chemicals (EDCs). Anogenital distance (AGD) is a hormone-dependent marker of reproductive system development.

We evaluated associations of maternal EDCs with infant AGD at birth and mini-puberty (5 months), and AGD growth across infancy.

Pregnant women enrolled in I-KIDS (Illinois Kids Development Study)-an observational longitudinal study (2013-2019).

Participants were recruited from two OBGyn clinics in Champaign-Urbana, IL.

This study includes 563 mother/infant pairs at birth and 5-months of age.

We measured 10 phthalates/replacements and nine phenols in five pooled first-morning urine samples collected across pregnancy.

In newborns and 5-month-olds, we divided short and long AGD measures by body length (termed anogenital index, AGI) and calculated %AGI growth across infancy. We evaluated covariate-adjusted associations of phthalates/replacements or phenols separately (quantile g-computation) or combined (hierarchical Bayesian kernel machine regression), with AGI measures.

Associations of phthalates/replacements with newborn AGI in females and phenols in males were inconsistent. However, in 5-month-old females, each quartile increase in the phthalate/replacement mixture was associated with -4.13 mm/m shorter AGIShort (95% confidence interval (CI): -7.22, -1.05), -3.89 mm/m shorter AGILong (95%CI: -7.55, -0.23), -39.49% less AGIShort growth (95%CI: -62.44, -16.54), and -8.78% less AGILong growth (95%CI: -16.06, -1.51); associations with AGILong growth were strongest at lower mixture quantiles.

AGD in mini-puberty and growth across infancy may reflect EDC-mediated hormonal disruption in utero, particularly in females, supporting the need to investigate these markers as predictors of long-term reproductive health.